Complete cytogenetic characterization of the human breast cancer cell line MA11 combining G-banding, comparative genomic hybridization, multicolor fluorescence in situ hybridization, RxFISH, and chromosome-specific painting

Abstract

The MA11 cell line was established from malignant cells isolated from the bone marrow of a breast cancer patient. It metastasizes selectively to the brain in athymic mice. Since the genomic rearrangements of only a few breast cancer cell lines have been characterized completely, we analyzed MA11 cytogenetically. Because the G-banding analysis revealed a very complex karyotype with several markers and chromosomes with additional material of unknown origin, we used multicolor fluorescence in situ hybridization (M-FISH), cross-species color banding (RxFISH), comparative genomic hybridization (CGH), and chromosome-specific probes to better characterize the chromosome abnormalities. The use of these FISH-based screening techniques allowed us to detect previously unsuspected chromosomal changes and determine the identity of chromosomal markers. Multicolor FISH was especially useful to identify the rearranged chromosomes, whereas RxFISH, G-banding, and CGH were instrumental in determining breakpoint positions, although some uncertainties were removed only after hybridization with chromosome-specific probes. The combined analysis revealed a near-triploid karyotype with no less than 20 chromosomes demonstrating structural rearrangements. The resulting imbalances included several of those known to be common in primary breast carcinomas (gain of 1q, 8q, and 20q and loss of 8p, 11q, and 13q), indicating that the MA11 cell line may serve as a good model to study breast carcinogenesis. The full cytogenetic characterization we present may guide future searches for the mechanism of organ-selective metastasis in this model system and, possibly, also in vivo.